Abstract
BackgroundA novel phenotype consisting of cataract, mental retardation, erythematous skin rash and facial dysmorphism was recently described in an extended pedigree of Australian Aboriginal descent. Large scale chromosomal re-arrangements had previously been ruled out. We have conducted a genome-wide scan to map the linkage region in this family.MethodsGenome-wide linkage analysis using Single Nucleotide Polymorphism (SNP) markers on the Affymetrix 10K SNP array was conducted and analysed using MERLIN. Three positional candidate genes (ZBTB17, EPHA2 and EPHB2) were sequenced to screen for segregating mutations.ResultsUnder a fully penetrant, dominant model, the locus for this unique phenotype was mapped to chromosome 1p35.3-p36.32 with a maximum LOD score of 2.41. The critical region spans 48.7 cM between markers rs966321 and rs1441834 and encompasses 527 transcripts from 364 annotated genes. No coding mutations were identified in three positional candidate genes EPHA2, EPHB2 or ZBTB17. The region overlaps with a previously reported region for Volkmann cataract and the phenotype has similarity to that reported for 1p36 monosomy.ConclusionsThe gene for this syndrome is located in a 25.6 Mb region on 1p35.3-p36.32. The known cataract gene in this region (EPHA2) does not harbour mutations in this family, suggesting that at least one additional gene for cataract is present in this region.
Highlights
A novel phenotype consisting of cataract, mental retardation, erythematous skin rash and facial dysmorphism was recently described in an extended pedigree of Australian Aboriginal descent
We recently described a novel phenotype in a large family of Australian Aboriginal descent [5]
The phenotype is characterised by developmental delay, short stature, childhood onset cortical cataract, facial dysmorphism, clinodactyly, thin hair and an erythematous skin rash
Summary
A novel phenotype consisting of cataract, mental retardation, erythematous skin rash and facial dysmorphism was recently described in an extended pedigree of Australian Aboriginal descent. Technology has advanced to the point where large-scale genome-wide association studies for complex diseases are feasible, family based disease gene discovery still plays an important role, in identifying the genetic causes of Mendelian disease [1]. We recently described a novel phenotype in a large family of Australian Aboriginal descent [5]. The phenotype is characterised by developmental delay, short stature, childhood onset cortical cataract, facial dysmorphism, clinodactyly, thin hair and an erythematous skin rash. The two mothers of the 5 affected male children displayed only a mild cortical cataract not yet requiring surgery and are of short stature, but do not display the other features. We have conducted a genome-wide linkage analysis to localise the gene for this distinctive phenotype
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call